Quadrant Field Pupillometry Detects Melanopsin Dysfunction in Glaucoma Suspects and Early Glaucoma

Adhikari, Prakash; Zele, Andrew J.; Thomas, Ravi; Feigl, Beatrix

doi:10.1038/srep33373

Cited by 74 publications

(99 citation statements)

References 98 publications

(161 reference statements)

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“…As for RGCs, ipRGC abnormalities have been reported in rodent models of experimental glaucoma [106][107][108][109] and in glaucomatous patients. 110,111 We reported an ~50%-70% reduction of RGC axon terminals (including ipRGCs) in several visual and nonvisual structures, notably in the SCN, and an alteration of the expression of opsin genes in the retina in an experimental rat model of glaucoma, 106 as observed by others. 112 In addition, several nonvisual responses to light were affected, such as the pupillary light response, light-induced nocturnal pineal melatonin suppression, and locomotor activity rhythm.…”

mentioning

confidence: 66%

The retinal clock in mammals: role in health and disease

Felder-Schmittbuhl¹,

Calligaro²,

Dkhissi-Benyahya³

2017

CPT

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Abstract:The mammalian retina contains an extraordinary diversity of cell types that are highly organized into precise circuits to perceive and process visual information in a dynamic manner and transmit it to the brain. Above this builds up another level of complex dynamic, orchestrated by a circadian clock located within the retina, which allows retinal physiology, and hence visual function, to adapt to daily changes in light intensity. The mammalian retina is a remarkable model of circadian clock because it harbors photoreception, self-sustained oscillator function, and physiological outputs within the same tissue. However, the location of the retinal clock in mammals has been a matter of long debate. Current data have shown that clock properties are widely distributed among retinal cells and that the retina is composed of a network of circadian clocks located within distinct cellular layers. Nevertheless, the identity of the major pacemaker, if any, still warrants identification. In addition, the retina coordinates rhythmic behavior by providing visual input to the master hypothalamic circadian clock in the suprachiasmatic nuclei (SCN). This light entrainment of the SCN to the light/dark cycle involves a network of retinal photoreceptor cells: rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). Although it was considered that these photoreceptors synchronized both retinal and SCN clocks, new data challenge this view, suggesting that none of these photoreceptors is involved in photic entrainment of the retinal clock. Because circadian organization is a ubiquitous feature of the retina and controls fundamental processes, the coherence from cell to tissue is critical for circadian functions, and disruption of retinal clock organization or its response to light can potentially have a major impact on retinal pathophysiology and vision.

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confidence: 66%

The retinal clock in mammals: role in health and disease

Felder-Schmittbuhl¹,

Calligaro²,

Dkhissi-Benyahya³

2017

CPT

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“…While their involvement in AMD is currently not fully understood, pilot data indicate that they are dysfunctional in late stages of the condition . Whether they are affected in early AMD as has been shown for glaucoma (Adhikari, Zele, Thomas & Feigl 2016b) and in diabetes without retinopathy (Feigl et al 2012b) is yet to be determined. The choroid lies posterior to the retina and is separated from the retinal pigment epithelium (RPE) by Bruch's membrane (BM).…”

Section: Statement Of Original Authorshipmentioning

confidence: 97%

“…IpRGCs have demonstrated enhanced survival after optic nerve injury and transection in rats (Li et al 2008;Perez de Sevilla Muller, Sargoy, Rodriguez & Brecha 2014) suggesting high injury resistance (Cui, Ren, Sollars, Pickard & So 2015), although studies in humans show ipRGC dysfunction in patients with glaucoma (Feigl, Mattes, Thomas & Zele 2011b;Gracitelli et al 2014;Kankipati, Girkin & Gamlin 2011) and more recently in glaucoma suspects (Adhikari et al 2016b). The initial evidence of altered ipRGC function in AMD is shown in a pilot study by , although little is known about the effect of AMD on ipRGC function in various stages of the disease.…”

Section: Intrinsically Photosensitive Retinal Ganglion Cell Functionmentioning

confidence: 99%

Image and Non-Image Forming Melanopsin Function in Age-Related Macular Degeneration

Maynard¹

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“…Using a Maxwellian view pupillometer and optimised stimulus paradigms that are robust in detecting subtle melanopsin defects (Adhikari et al, 2015b;Adhikari et al, 2016b), the present study tests the hypothesis that individuals with non-seasonal depression have reduced PIPR and PLR amplitudes that are associated with lower daily ambient light exposure levels compared to the healthy individuals. The study further examines the hypothesis that patients with non-seasonal depression have reduced visual contrast sensitivity than healthy people.…”

Section: Chapter 1: Introductionmentioning

confidence: 94%

“…The measurement of the PIPR allows for the direct and in vivo assessment of ipRGC function in humans (Adhikari et al, 2015b;Feigl & Zele, 2014;Gamlin et al, 2007;Kankipati et al, 2010;Markwell et al, 2010;McDougal et al, 2010;Young et al, 2008). Collectively, the PIPR has been assessed as a direct and non-invasive biomarker of ipRGC function in human eyes with and without retinal disease (Adhikari, Zele, Thomas, & Feigl, 2016b;Feigl, Mattes, Thomas, & Zele, 2011;Feigl et al, 2014;Feigl, Zele, Fader, Howes, Hughes, Jones, & Jones, 2012;Kankipati et al, 2010;Kankipati, Girkin, & Gamlin, 2011;Kelbsch, Maeda, Strasser, Blumenstock, Wilhelm, Wilhelm, & Peters, 2016;Markwell et al, 2010;Maynard, Zele, & Feigl, 2015) and therefore can also be used to measure the input of ipRGC projections to the brain mood centres to evaluate the melanopsin function in depressive disorders (Laurenzo et al, 2016;Roecklein et al, 2013).…”

Section: Chapter 1: Introductionmentioning

confidence: 99%

An Evaluation of Melanopsin Function and Light Exposure in Depressive Disorders

Ojha¹

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Aberrant light exposure causes depression in animals through a pathway involving the recently discovered intrinsically photosensitive Retinal Ganglion Cells (ipRGCs). The photopigment melanopsin expressed in ipRGCs encodes irradiance to signal to the nonimage-forming centres of the brain, including the suprachiasmatic nucleus (SCN) for circadian photoentrainment and the olivary pretectal nucleus (OPN) to control the pupil light reflex. Mouse models have further identified ipRGC projections to the brain nuclei that regulate mood and behaviour. In humans, the post-illumination pupil response (PIPR), a sustained pupillary constriction after light offset, is used as a direct and non-invasive biomarker of ipRGC function.The PIPR amplitude is reduced in humans with seasonal affective disorder (SAD) that shows a seasonal variation in depressive episodes with a peak manifestation in winter when the solar light exposure is low, but a recent study including patients with non-seasonal depressive disorder did not detect ipRGC dysfunction. Moreover, neither study measured the ambient light exposure levels in patients with depression for comparison to healthy individuals without depression. The knowledge of the role of light coding cells (ipRGCs) in major depressive disorder (MDD) is incomplete unless the relationship between ambient light exposure levels and melanopsin function is evaluated. This study aims to measure the environmental light exposure levels and their relationship with melanopsin-mediated PIPR in non-seasonal depression. It is hypothesised that the patients with non-seasonal depression are exposed to low light levels and this is associated with impaired melanopsin function.A sample of 22 adults was recruited, including people with non-seasonal depression (n = 8, median age: 35 years) and healthy age-matched controls (n = 14, median age: 29 years).The presence of a DSM-IV MDD was assessed using the Mini International Neuropsychiatry ii Interview (MINI 6). The severity of depression symptoms was assessed with the Beck Depression Inventory (BDI-II). Individuals with recurrent MDD assessed with the MINI and a positive screen on the Seasonal Pattern Assessment Questionnaire and the Hamilton Depression Rating Scale-SAD (HDRS-SAD) were excluded as SAD. Both groups had visual acuity ≥ 6/6, normal colour vision and intraocular pressure (IOP) ≤ 21 mmHg, no corneal and lenticular opacities and normal retinae and optic discs. The ipRGC-mediated PIPR was measured using a short duration (1 s) high irradiance (15.5 log quanta.cm -2 .s -1 ) short wavelength (blue appearing) light stimulus with a custom built Maxwellian view pupillometer. Light exposure levels, sleep-wake times and sleep efficiency were determined over 2 weeks with an ambulatory light sensor device (Geneactive).The mean daily light exposure levels were similar between the groups and there were no statistically significant differences between the groups for light exposure levels as a function of clock hours, nor in the total number of minutes of exposu...

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Quadrant Field Pupillometry Detects Melanopsin Dysfunction in Glaucoma Suspects and Early Glaucoma

Cited by 74 publications

References 98 publications

The retinal clock in mammals: role in health and disease

The retinal clock in mammals: role in health and disease

Image and Non-Image Forming Melanopsin Function in Age-Related Macular Degeneration

An Evaluation of Melanopsin Function and Light Exposure in Depressive Disorders

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